[Precision medicine enhances personalized medicine in cardiology]. / Präzisionsmedizin vertieft die personalisierte Medizin in der Kardiologie.

Personalized medicine and precision medicine, frequently used synonymously, shall be clearly differentiated. Accordingly, personalization in cardiac medicine is based on the clinical presentation of a patient, as well as his/her cardiovascular risk factors and comorbidities, electrocardiography, imaging, and biomarkers for myocardial load and ischemia. Personalization is based on large clinical trials with detailed subgroup analyses and is practiced on the basis of guidelines. Further in depth personalization is achieved by precision medicine, which is based on innovative imaging for myocardial structure, coronary morphology, and electrophysiology. From the clinical perspective, genome analyses are relevant for comparatively rare monogenetic cardiovascular diseases. While these as well as transcriptome and metabolome analyses play a significant role in cardiovascular research with great translation potential, they have not yet been broadly introduced in the diagnosis, prevention, and treatment of complex cardiovascular diseases. Furthermore, digital technologies have considerable potential in cardiovascular precision medicine. On the one hand, this is based on the frequency of the diseases with the availability of Big Data and, on the other hand, on the availability of bio-signals and sensors of those signals in cardiovascular diseases.

Intrarenal Doppler ultrasonography in patients with HFrEF and acute decompensated heart failure undergoing recompensation.

OBJECTIVES: Renal venous congestion due to backward heart failure leads to disturbance of renal function in acute decompensated heart failure (ADHF). Whether decongestion strategies have an impact on renal venous congestion is unknown. Objective was to evaluate changes in intrarenal hemodynamics using intrarenal Doppler ultrasonography (IRD) in patients with heart failure with reduced ejection fraction (HFrEF) and ADHF undergoing recompensation. METHODS: Prospective observational study in patients with left ventricular ejection fraction (LV-EF) ≤ 35% hospitalized due to ADHF. IRD measurement was performed within the first 48 h of hospitalisation and before discharge. Decongestion strategies were based on clinical judgement according to heart failure guidelines. IRD was used to assess intrarenal venous flow (IRVF) pattern, venous impedance index (VII) and resistance index (RI). Laboratory analyses included plasma creatinine, eGFR and albuminuria. RESULTS: A number of 35 patients with ADHF and LV-EF ≤ 35% were included into the study. IRD could be performed in 30 patients at inclusion and discharge. At discharge, there was a significant reduction of VII from a median of 1.0 (0.86-1.0) to 0.59 (0.26-1.0) (p < 0.01) as well as improvement of IRVF pattern categories (p < 0.05) compared to inclusion. Albuminuria was significantly reduced from a median of 78 mg/g creatinine (39-238) to 29 mg/g creatinine (16-127) (p = 0.02) and proportion of patients with normoalbuminuria increased (p = 0.01). Plasma creatinine and RI remained unchanged (p = 0.73; p = 0.43). DISCUSSION: This is the first study showing an effect of standard ADHF therapy on parameters of renal venous congestion in patients with HFrEF and ADHF. Doppler sonographic evaluation of renal venous congestion might provide additional information to guide decongestion strategies in patients with ADHF.

Resting and exercise haemodynamic characteristics of patients with advanced heart failure and preserved ejection fraction.

AIMS: This study aimed to describe haemodynamic features of patients with advanced heart failure with preserved ejection fraction (HFpEF) as defined by the Heart Failure Association (HFA) of the European Society of Cardiology (ESC). METHODS AND RESULTS: We used pooled data from two dedicated HFpEF studies with invasive exercise haemodynamic protocols, the REDUCE LAP-HF (Reduce Elevated Left Atrial Pressure in Patients with Heart Failure) trial and the REDUCE LAP-HF I trial, and categorized patients according to advanced heart failure (AdHF) criteria. The well-characterized HFpEF patients were considered advanced if they had persistent New York Heart Association classification of III-IV and heart failure (HF) hospitalization < 12 months and a 6 min walk test distance < 300 m. Twenty-four (22%) out of 108 patients met the AdHF criteria. On evaluation, clinical characteristics and resting haemodynamics were not different in the two groups. Patients with AdHF had lower work capacity compared with non-advanced patients (35 ± 16 vs. 45 ± 18 W, P = 0.021). Workload-corrected pulmonary capillary wedge pressure normalized to body weight (PCWL) was higher in AdHF patients compared with non-advanced (112 ± 55 vs. 86 ± 49 mmHg/W/kg, P = 0.04). Further, AdHF patients had a smaller increase in cardiac index during exercise (1.1 ± 0.7 vs. 1.6 ± 0.9 L/min/m2 , P = 0.028). CONCLUSIONS: A significantly higher PCWL and lower cardiac index reserve during exercise were observed in AdHF patients compared with non-advanced. These differences were not apparent at rest. Therapies targeting the haemodynamic compromise associated with advanced HFpEF are needed.

[Less is more in cardiology and angiology]. / Weniger ist mehr in Kardiologie und Angiologie.

Cardiovascular medicine is one of the most resource-consuming parts of the healthcare system and many examples of overdiagnostic and overtreatment can be found. The present article presents just three of these, one from cardiology and two from vascular medicine. The topic of chronic coronary heart disease concerns the unequivocal proof of ischemia before a coronary intervention. The sections on Duplex sonography of the cervical blood vessels and the diagnostics of thrombophilia describe which valid clinical problems may justify the performance of these examinations at all. The potential for harm caused by overdiagnostics in both cases lies not only in the unnecessary use of resources but, more importantly, in the subsequent overtreatment. The few appropriate indications are described in detail.

Atrial fibrillation is frequent but does not affect risk stratification in pulmonary embolism.

BACKGROUND: Although prior studies indicate a high prevalence of atrial fibrillation (AF) in patients with pulmonary embolism (PE), the exact prevalence and prognostic impact are unknown. METHODS: We aimed to investigate the prevalence, risk factors and prognostic impact of AF on risk stratification, in-hospital adverse outcomes and mortality in 528 consecutive PE patients enrolled in a single-centre registry between 09/2008 and 09/2017. RESULTS: Overall, 52 patients (9.8%) had known AF and 57 (10.8%) presented with AF on admission; of those, 34 (59.6%) were newly diagnosed with AF. Compared to patients with no AF, overt hyperthyroidism was associated with newly diagnosed AF (OR 7.89 [2.99-20.86]), whilst cardiovascular risk comorbidities were more frequently observed in patients with known AF. Patients with AF on admission had more comorbidities, presented more frequently with tachycardia and elevated cardiac biomarkers and were hence stratified to higher risk classes. However, AF on admission had no impact on in-hospital adverse outcome (8.3%) and in-hospital mortality (4.5%). In multivariate logistic regression analyses corrected for AF on admission, NT-proBNP and troponin elevation as well as higher risk classes in risk assessment models remained independent predictors of an in-hospital adverse outcome. CONCLUSION: Atrial fibrillation is a frequent finding in PE, affecting more than 10% of patients. However, AF was not associated with a higher risk of in-hospital adverse outcomes and did not affect the prognostic performance of risk assessment strategies. Thus, our data support the use of risk stratification tools for patients with acute PE irrespective of the heart rhythm on admission.

[Apps in General Medicine : A topic for medical education?​]. / Apps in der Inneren Medizin : Ein Thema für das Medizinstudium?

BACKGROUND: Health-related apps can provide helpful resources for both doctors and patients. The selection of potentially useful apps and the appraisal of their quality are particularly important in the context of medicine as false or confusing app content may put patients at risk. AIM: In this article a brief overview of the topic is provided and the results of a pilot study, in which medical students tested and evaluated the quality of 143 health-related apps on the topics of cardiology and pulmonology are presented. MATERIAL AND METHODS: Using the semiautomated retrospective app store analysis (SARASA) method, a group of apps concerned with cardiology and pulmonology were identified from a pool of over 2,000,000 apps available in the Apple Store. As part of a practical exercise, 138 4th year medical students tested a total of 143 of these apps, subsequently evaluating them using a specially devised questionnaire. RESULTS: The most frequent target population among the tested apps was identified as patients and their carers and the primary purpose in the majority of cases was the provision of information. Despite this, at least one quarter of all apps tested required users to enter sensitive health-related information. The evaluations by the students portrayed a large range in terms of the quality of the apps tested. DISCUSSION: Health-related apps play a growing role in the management of illnesses in the field of internal medicine. Doctors must be aware of the benefits and limitations of using such apps and should be prepared during their medical studies for the challenge of advising patients on this topic.

[Diagnosis and treatment of aortic valve stenosis]. / Diagnose und Therapie der Aortenklappenstenose.

Aortic valve stenosis (AS) is the most frequently observed valvular heart disease. Once it is symptomatic the mortality rapidly increases. The diagnostic gold standard is transthoracic echocardiography. By measuring the maximum transvalvular velocity, mean transaortic pressure gradient and aortic valve opening area, classification of the type of stenosis can be defined. A differentiation is made between high-gradient AS, low-flow low gradient AS with reduced ventricular ejection fraction (<50%) and the paradoxical low-flow low-gradient AS with preserved ventricular function (≥50%). In some cases, additional diagnostic tools are necessary using dobutamine stress echocardiography, transesophageal echocardiography and cardiac computed tomography. The treatment follows an individualized approach. In cases of indications for valve replacement the multidisciplinary heart team takes into account the patient's age and individual risk for deciding whether an open surgical approach or transcatheter aortic valve implantation is indicated.

[InterAtrial Shunt Device in diastolic heart failure]. / InterAtrial Shunt Device bei diastolischer Herzinsuffizienz.

All types of heart failure are associated with reduced cardiac output and/or increased left atrial (LA) pressure. In diastolic heart failure (heart failure with preserved ejection fraction [HFpEF]), the increased LA pressure plays a central role, leading to pulmonary venous hypertension (PVH) and increased pulmonary artery pressure. These pressure parameters are presumably decisive for the symptoms and mortally of heart failure, particularly of the diastolic form. This is the basis for treatment with an interarterial shunt to reduce LA pressure in patients with diastolic heart failure and PVH. At first glance, this appears paradoxical, since closure of an atrial septum defect serves to prevent increased pulmonary vascular resistance and paradoxical embolism. Prevention of increased pulmonary vascular resistance and paradoxical embolism is thus an essential aspect in the development of devices for establishing an interarterial shunt. Reports on the InterAtrial Shunt Device (IASD®) and the V­Wave have been published, both of which can be implanted with a low risk and few complications. The V­Wave device is equipped with a valve to prevent paradoxical embolisms. However, paradoxical embolisms were also not observed with the IASD®, and the valve of the V­Wave exhibited considerable degenerative changes and valve closure. Hemodynamic and clinical data of patients with an IASD® or an open V­Wave device demonstrated a sustained hemodynamic improvement. Physical performance capacity and quality of life were increased. Whether IASD® may be broadly applicable in patients with diastolic heart failure is currently under investigation. In selected highly symptomatic patients with diastolic heart failure and PVH, the IASD® is already in clinal use.

[Modern genetic counselling : Practical aspects exemplified by hypertrophic cardiomyopathy]. / Moderne humangenetische Beratung : Praktische Aspekte am Beispiel der hypertrophen Kardiomyopathie.

Genetic counselling and subsequent molecular genetic testing should be performed in patients when an inherited monogenic form of heart disease is suspected. For the individual patient as well as for the (possibly asymptomatic) relatives, molecular diagnostics is important for an early diagnosis, (preventive) therapy and prognosis assessment. Using the example of hypertrophic cardiomyopathy (HCM), the most common monogenic form of structural heart disease, essential aspects of modern genetic counselling are elucidated. Specific examples of one case with a classical form of hypertrophic obstructive cardiomyopathy and one case of congenital HCM with Noonan's syndrome are discussed.

Electromechanical vortex filaments during cardiac fibrillation.

The self-organized dynamics of vortex-like rotating waves, which are also known as scroll waves, are the basis of the formation of complex spatiotemporal patterns in many excitable chemical and biological systems. In the heart, filament-like phase singularities that are associated with three-dimensional scroll waves are considered to be the organizing centres of life-threatening cardiac arrhythmias. The mechanisms that underlie the onset, maintenance and control of electromechanical turbulence in the heart are inherently three-dimensional phenomena. However, it has not previously been possible to visualize the three-dimensional spatiotemporal dynamics of scroll waves inside cardiac tissues. Here we show that three-dimensional mechanical scroll waves and filament-like phase singularities can be observed deep inside the contracting heart wall using high-resolution four-dimensional ultrasound-based strain imaging. We found that mechanical phase singularities co-exist with electrical phase singularities during cardiac fibrillation. We investigated the dynamics of electrical and mechanical phase singularities by simultaneously measuring the membrane potential, intracellular calcium concentration and mechanical contractions of the heart. We show that cardiac fibrillation can be characterized using the three-dimensional spatiotemporal dynamics of mechanical phase singularities, which arise inside the fibrillating contracting ventricular wall. We demonstrate that electrical and mechanical phase singularities show complex interactions and we characterize their dynamics in terms of trajectories, topological charge and lifetime. We anticipate that our findings will provide novel perspectives for non-invasive diagnostic imaging and therapeutic applications.